Synthesis of Sulfoximidoyl-Substituted Triazoles by Huisgen 1,3-Dipolar Cycloaddition

Bernhard Füger; Genia Sklute; Ilan Marek; Gae Young Bolm; Carsten Bolm

doi:10.1055/s-2007-1000837

LETTER

Synthesis of Sulfoximidoyl-Substituted Triazoles by Huisgen 1,3-Dipolar Cycloaddition

Bernhard Füger^a, Genia Sklute^b, Ilan Marek^b, Gae Young Bolm^a, Carsten Bolm*^a
^a Institut für Organische Chemie, RWTH Aachen, Landoltweg 1, 52056 Aachen, Germany
Fax: +49(241)8092391; e-Mail: Carsten.Bolm@oc.rwth-aachen.de;
^b The Mallat Family Laboratory of Organic Chemistry, Schulich Faculty of Chemistry and The Lise Meitner-Minerva Center for Computational Quantum Chemistry, Technion-Israel Institute of Technology, Haifa 32 000, Israel

Abstract

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Abstract

The reaction of alkynyl sulfoximines with in situ prepared organic azides in water-dichloromethane under reflux affords sulfoximidoyl-substituted triazoles by Huisgen 1,3-dipolar cycloaddition.

Key words

azide - cycloaddition - Huisgen - sulfoximines - triazole

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References

References and Notes

For selected recent contributions, see:

<A NAME="RG33307ST-1A">1a</A> Reggelin M. Kuehl J. Kaiser JP. Buehle P. Synthesis 2006, 2224

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Reviews:

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<A NAME="RG33307ST-3B">3b</A> Okamura H. Bolm C. Chem. Lett. 2004, 33: 482

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<A NAME="RG33307ST-5C">5c</A> Luecking U, Nguyen D, von Bonin A, von Ahsen O, Krueger M, Briem H, Kettschau H, Prien O, Mengel A, Krolikiewicz K, Boemer U, Bothe U, and Hartung I. inventors; WO 071455 A1. ; Schering AG

<A NAME="RG33307ST-5D">5d</A> Luecking U. inventors; EP 1 710 246 A1. ; Schering AG

<A NAME="RG33307ST-5E">5e</A> Luecking U, Bader B, and Siemeister G. inventors; EP 1 803 723 A1. ; Bayer Schering Pharma

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Refs 6 and 7.

In the reactions reported here, racemic sulfoximines were used.

The interactions between the benzylic hydrogens and the hydrogens of the alkyl or alkoxy chain in the ¹H-NOESY spectra also confirmed the molecular structures of triazole derivatives 3b-e,g,h. Although present in the crude product mixtures, the other regioisomers (triazoles 5) could never be obtained in pure form (Figure [1] ).

Figure 1

General Procedure for the Cycloaddition ReactionUnder vigorous stirring a mixture of NaN₃ (12 equiv) and the corresponding bromide (15 equiv) was heated to reflux in H₂O (0.7 M) for 1 h. Then, a solution of sulfoximine 4 (1 equiv) in CH₂Cl₂ (0.08 M) was added dropwise. After 3 h at 100 °C under reflux and stirring, the product was extracted with CH₂Cl₂ and purified by flash column chromatography. As representative example, the analytical data for 1-benzyl-5-butyl-4-(N-tosyl)-(4-methylphenylsulfonimidoyl)-1H-1,2,3-triazole (3a) obtained from the reaction of sulfoximine 4a with benzyl azide are given. Colorless oil (68%); chromatography: EtOAc-pentane (1:3). ¹H NMR (400 MHz, CDCl₃): δ = 0.79 (t, J = 7.0 Hz, 3 H), 1.21-1.29 (m, 4 H), 2.37 (s, 3 H), 2.41 (s, 3 H), 2.76-2.85 (m, 1 H), 2.93-3.02 (m, 1 H), 5.44 (d, J = 15.5 Hz, 1 H), 5.49 (d, J = 15.5 Hz, 1 H), 7.14-7.18 (m, 2 H), 7.20 (d, J = 8.0 Hz, 2 H), 7.31-7.35 (m, 5 H), 7.80 (d, J = 8.3 Hz, 2 H), 7.98 (d, J = 8.5 Hz, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 13.6 (CH₃), 21.5 (CH₃), 21.7 (CH₃), 22.7 (CH₂), 23.0 (CH₂), 30.5 (CH₂), 52.5 (CH₂), 126.5 (CH), 127.2 (CH), 128.2 (CH), 128.7 (CH), 129.0 (2 × CH), 129.9 (CH), 133.5 (C), 135.2 (C), 140.4 (C), 141.4 (C), 141.9 (C), 142.6 (C), 145.4 (C). IR (CHCl₃): ν = 2959 (m), 1454 (m), 1318 (m), 1243 (m), 1096 (s), 1018 (m), 757 (s), 540 (m). MS (CI): m/z (relative intensity) = 523 (6) [M + H]⁺. Anal. Calcd for C₂₇H₃₀N₄S₂O₃: C, 62.04; H, 5.79; N, 10.72. Found: C, 62.06; H, 5.81; N, 11.14.